272 research outputs found

    Non-targeted analysis of the grapevine leaf metabolome

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    Aqueous Redox Flow Battery Suitable for High Temperature Applications Based on a Tailor‐Made Ferrocene Copolymer

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    Abstract Water‐soluble, and ferrocene‐containing methacrylamide copolymers with different comonomer ratios of the solubility‐promoting comonomer [2‐(methacryloyloxy)‐ethyl]‐trimethylammonium chloride (METAC) are synthesized in order to obtain a novel, temperature‐stable electrolyte for aqueous redox flow batteries. The electrochemical properties of one chosen polymer are studied in detail by cyclic voltammetry and rotating disc electrode (RDE) investigations. Additionally, the diffusion coefficient and the charge transfer rate are obtained from these measurements. The diffusion coefficient from RDE is compared to the value from synthetic boundary experiments at battery concentrations, using an analytical ultracentrifuge, yielding diffusion coefficients of a similar order of magnitude. The polymer is further tested in a redox flow battery setup. While performing charge and discharge experiments against the well‐established bis ‐(trimethylammoniumpropyl)‐viologen, the polymer reveals high columbic efficiencies of >99.8% and desirable apparent capacity retention, both at room temperature as well as at 60 °C. Further experiments are conducted to verify the stability of the active compounds under these conditions in both charge states. Lastly, the electrochemical behavior is linked to the characteristics of the polymers concerning absolute values of the molar mass and diffusion coefficients.A new ferrocene containing monomer is synthesized and its copolymerization with a water‐solubility promoting comonomer is investigated. The electrochemical and solution characteristics of a corresponding polymer are studied in detail. With a coulombic efficiency of >99.8% in an aqueous redox flow battery setup at 60 °C, a cheap, robust system for use at elevated temperatures is presented. imag

    A viologen polymer and a compact ferrocene: Comparison of solution viscosities and their performance in a redox flow battery with a size exclusion membrane

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    In this work, the synthesis and characterization of a compact, ferrocene tetramer and a linear viologen polymer is reported. The latter material is a new, 4,4′‐bipyridine containing, organo‐soluble polymer. As aimed for solubility in nonpolar solvents, a 2‐ethylhexyl‐moiety to promote organosolubility and 4‐vinylbenzyl serving as a polymerizable group are introduced to a 4,4′‐bipyridine. The halide anions of the monomer cation are exchanged to bis(trifluoromethansulfon)imide, which further enhances organosolubility. The monomer is subsequently copolymerized with styrene by free radical polymerization. In addition, a four‐ferrocene‐containing compact structure, based on pentaerythritol, is synthesized via the straightforward radical thiol‐ene reaction. The polymer solutions are thoroughly characterized hydrodynamically. Subsequently, propylene carbonate‐based solutions of both materials are prepared to allow an assessment for future energy storage applications. This is done by testing battery characteristics in a custom‐made flow‐cell with a simple dialysis membrane for physical separation of the active materials. The capability of energy storage is verified by leaving the charged materials in solution in an open circuit for 24 h. Here, more than 99% of the stored charges can be recovered. Cycling the battery for 100 times reveals the remarkable stability of the materials of only 0.2% capacity loss per day in the battery setup

    Chronic pain in primary care. German figures from 1991 and 2006

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    <p>Abstract</p> <p>Background</p> <p>Until now only limited research has been done on the prevalence of chronic pain in primary care. The aim of this investigation was to study the health care utilisation of patients suffering from pain. How many patients visit an outpatient clinic because of the symptom of pain? These data were compared with data from a similar study in 1991, to investigate whether improvements had been achieved.</p> <p>Methods</p> <p>A total of 1201 consecutive patients visiting outpatient clinics were surveyed in six practices in the western part of Germany on randomly selected days by means of questionnaires. Topics were the point prevalence of pain and the period prevalence of chronic pain, its characteristics and its impact on daily life, as well as data on previous therapies for pain. A retrospective comparison was made with the data from a similar study with same design surveying 900 patients that took place in five practices during 1991.</p> <p>Results</p> <p>In 2006, pain was the main reason for consulting a doctor in 42.5% of all patients (1991: 50.3%). Of all respondents, 62% suffered from pain on the particular day of the consultation, and 40% reported that they had been suffering from pain for more than six months (1991: 36.4%). As many as 88.3% of patients with chronic pain reported a negative impact on their daily life due to this pain (1991: 68%), and 88.1% reported impairment of their working life because of chronic pain (1991: 59.1%).</p> <p>Conclusion</p> <p>Pain, and chronic pain in particular, is a central problem in primary care. Over the last 15 years, the number of patients suffering from chronic pain has not decreased. In nearly half of all cases, pain is still the reason for health care utilisation in outpatient clinics. Pain represents a major primary health care problem with enormous impact on public health. Improvements can only be achieved by improving the quality of health care at the primary care level.</p

    Kank Is an EB1 Interacting Protein that Localises to Muscle-Tendon Attachment Sites in Drosophila

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    Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role in the regulation of microtubule plus ends. It directly binds to microtubule plus ends and recruits proteins which regulate microtubule dynamics and behaviour. We report the identification of Kank, the sole Drosophila orthologue of human Kank proteins, as an EB1 interactor that predominantly localises to embryonic attachment sites between muscle and tendon cells. Human Kank1 was identified as a tumour suppressor and has documented roles in actin regulation and cell polarity in cultured mammalian cells. We found that Drosophila Kank binds EB1 directly and this interaction is essential for Kank localisation to microtubule plus ends in cultured cells. Kank protein is expressed throughout fly development and increases during embryogenesis. In late embryos, it accumulates to sites of attachment between muscle and epidermal cells. A kank deletion mutant was generated. We found that the mutant is viable and fertile without noticeable defects. Further analysis showed that Kank is dispensable for muscle function in larvae. This is in sharp contrast to C. elegans in which the Kank orthologue VAB-19 is required for development by stabilising attachment structures between muscle and epidermal cells

    SNAI1 and SNAI2 Are Asymmetrically Expressed at the 2-Cell Stage and Become Segregated to the TE in the Mouse Blastocyst

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    SNAI1 and SNAI2 are transcription factors that initiate Epithelial-to-Mesenchymal cell transitions throughout development and in cancer metastasis. Here we show novel expression of SNAI1 and SNAI2 throughout mouse preimplantation development revealing asymmetrical localization of both SNAI1 and SNAI2 in individual blastomeres beginning at the 2-cell stage through to the 8-cell stage where SNAI1 and SNAI2 are then only detected in outer cells and not inner cells of the blastocyst. This study implicates SNAI1 and SNAI2 in the lineage segregation of the trophectoderm and inner cell mass, and provides new insight into these oncogenes

    Notch signaling in mouse blastocyst development and hatching

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    Research Areas: Developmental BiologyBackground: Mammalian early embryo development requires a well-orchestrated interplay of cell signaling pathways. Notch is a major regulatory pathway involved in cell-fate determination in embryonic and adult scenarios. However, the role of Notch in embryonic pre-implantation development is controversial. In particular, Notch role on blastocyst development and hatching remains elusive, and a complete picture of the transcription and expression patterns of Notch components during this time-period is not available. Results: This study provided a comprehensive view on the dynamics of individual embryo gene transcription and protein expression patterns of Notch components (receptors Notch1–4; ligands Dll1 and Dll4, Jagged1–2; and effectors Hes1–2), and their relationship with transcription of gene markers of pluripotency and differentiation (Sox2, Oct4, Klf4, Cdx2) during mouse blastocyst development and hatching. Transcription of Notch1–2, Jagged1–2 and Hes1 was highly prevalent and dynamic along stages of development, whereas transcription of Notch3–4, Dll4 and Hes2 had a low prevalence among embryos. Transcription levels of Notch1, Notch2, Jagged2 and Hes1 correlated with each other and with those of pluripotency and differentiation genes. Gene transcription was associated to protein expression, except for Jagged2, where high transcription levels in all embryos were not translated into protein. Presence of Notch signaling activity was confirmed through nuclear NICD and Hes1 detection, and downregulation of Hes1 transcription following canonical signaling blockade with DAPT. In vitro embryo culture supplementation with Jagged1 had no effect on embryo developmental kinetics. In contrast, supplementation with Jagged2 abolished Jagged1 transcription, downregulated Cdx2 transcription and inhibited blastocyst hatching. Notch signaling blockade by DAPT downregulated transcription of Sox2, and retarded embryo hatching. Conclusion: Transcription of Notch genes showed a dynamic pattern along blastocyst development and hatching. Data confirmed Notch signaling activity, and lead to the suggestion that Notch canonical signaling may be operating through Notch1, Notch3, Jagged1 and Hes1. Embryo culture supplementation with Jagged1 and Jagged2 unveiled a possible regulatory effect between Jagged1, Cdx2 and blastocyst hatching. Overall, results indicate that a deregulation in Notch signaling, either by its over or under-activation, affects blastocyst development and hatching.info:eu-repo/semantics/publishedVersio

    Brg1 Is Required for Cdx2-Mediated Repression of Oct4 Expression in Mouse Blastocysts

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    During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates that suppression of Oct4 expression in the trophectoderm is mediated by Cdx2. Nonetheless, the underlying epigenetic modifiers required for Cdx2-dependent repression of Oct4 are largely unknown. Here we show that the chromatin remodeling protein Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts. By employing a combination of RNA interference (RNAi) and gene expression analysis we found that both Brg1 Knockdown (KD) and Cdx2 KD blastocysts exhibit widespread expression of Oct4 in the trophectoderm. Interestingly, in Brg1 KD blastocysts and Cdx2 KD blastocysts, the expression of Cdx2 and Brg1 is unchanged, respectively. To address whether Brg1 cooperates with Cdx2 to repress Oct4 transcription in the developing trophectoderm, we utilized preimplantation embryos, trophoblast stem (TS) cells and Cdx2-inducible embryonic stem (ES) cells as model systems. We found that: (1) combined knockdown (KD) of Brg1 and Cdx2 levels in blastocysts resulted in increased levels of Oct4 transcripts compared to KD of Brg1 or Cdx2 alone, (2) endogenous Brg1 co-immunoprecipitated with Cdx2 in TS cell extracts, (3) in blastocysts Brg1 and Cdx2 co-localize in trophectoderm nuclei and (4) in Cdx2-induced ES cells Brg1 and Cdx2 are recruited to the Oct4 promoter. Lastly, to determine how Brg1 may induce epigenetic silencing of the Oct4 gene, we evaluated CpG methylation at the Oct4 promoter in the trophectoderm of Brg1 KD blastocysts. This analysis revealed that Brg1-dependent repression of Oct4 expression is independent of DNA methylation at the blastocyst stage. In toto, these results demonstrate that Brg1 cooperates with Cdx2 to repress Oct4 expression in the developing trophectoderm to ensure normal development

    Wdr74 Is Required for Blastocyst Formation in the Mouse

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    Preimplantation is a dynamic developmental period during which a combination of maternal and zygotic factors program the early embryo resulting in lineage specification and implantation. A reverse genetic RNAi screen in mouse embryos identified the WD Repeat Domain 74 gene (Wdr74) as being required for these critical first steps of mammalian development. Knockdown of Wdr74 results in embryos that develop normally until the morula stage but fail to form blastocysts or properly specify the inner cell mass and trophectoderm. In Wdr74-deficient embryos, we find activated Trp53-dependent apoptosis as well as a global reduction of RNA polymerase I, II and III transcripts. In Wdr74-deficient embryos blocking Trp53 function rescues blastocyst formation and lineage differentiation. These results indicate that Wdr74 is required for RNA transcription, processing and/or stability during preimplantation development and is an essential gene in the mouse

    HOXB4 Gene Expression Is Regulated by CDX2 in Intestinal Epithelial Cells

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    The mammalian Caudal-related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox (HOX) genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of HOXB4 gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether HOXB4 gene expression is regulated by CDX2 in the intestinal epithelium. We demonstrated binding of CDX2 to four different CDX2 binding sites in an enhancer region located upstream of the HOXB4 transcription start site. Mutations in the CDX2 binding sites reduced HOXB4 gene activity, and knock down of endogenous CDX2 expression by shRNA reduced HOXB4 gene expression. This is the first report demonstrating the CDX2 regulation of HOXB4 gene expression in the developed intestinal epithelium, indicating a possible role for HOXB4 in intestinal homeostasis
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